Effects of Vitamin D on Inflammation in Liver Disease

Veterans Medical Research Foundation

Status and phase: Unknown; Phase 2

Conditions: Vitamin D Deficiency; Hepatitis C Infection

Treatments: Drug: Vitamin D; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT01754961

UCSD-111219

Details and patient eligibility

About

Chronic liver diseases are associated with inflammation. The investigators postulate that Vitamin D may modulate inflammation. Thus the investigators will study the effect of Vitamin D replacement in patients with Hepatitis C infection and Vitamin D deficiency.

Full description

Vitamin D appears to be a critical signaling molecule for macrophages because is needed for activation and differentiation of monocytes/macrophages. From our Preliminary Studies( VA Merit Review Grant), we propose that Vitamin D deficiency may alter the 'pro-inflammatory' ('classically activated') M1 macrophages , characterized by i] high expression of NOS2, TNF-a, IL-1, IL-6, IL-8, TGF-a, CXCL10, and CCL19; and ii] minimal expression of arginase 1 and mannose R.

The clinical relevance of these findings is suggested by the presence of activated M1 macrophages in liver biopsies from patients with severe drug-induced liver injury (unpublished observations).

Prospective vitamin D supplementation studies with appropriate endpoints are needed to define the role of vitamin D on inflammation in patients with chronic liver diseases.

Enrollment: 24 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Men or women aged 18 or older
• Total 25-OH Vit D < 25 ng/mL
• Infection with HCV genotype 1 (subjects infected with multiple genotypes are not eligible).
• Plasma HCV RNA concentration of >100,000 IU/mL.
• HCV-infected subjects naïve to treatment: subjects who either have never been treated for HCV infection or who previously received HCV treatment ending > 3 months prior to enrollment (including, any IFN-Alpha with or without ribavirin, or other anti-HCV antiviral medication).

Exclusion criteria

• Women who are pregnant or breastfeeding.
• Patients with Sarcoidosis, Histoplasmosis, Lymphoma, Primary Hyperparathyroidism or Idiophatic Hypercalcemia.
• Liver Cirrhosis.
• Known active gastrointestinal disease that could interfere with the absorption of the test article.
• Laboratory determinations at screening as follows:
• Hemoglobin <10 g/dL .
• Serum creatinine that is not within normal limits. However, such subjects may be enrolled if the Cockroft-Gault glomerular filtration rate (GFR) is > 50 mL/minute.
• Unstable hypertension, cardiac disease or type 2 diabetes requiring changes in treatment with medications 4 weeks prior to screening or during the screening period.
• Use of an investigational drug within 4 weeks before the screening visit or during the screening period.
• Use of systemic immunosuppressants (including systemic, oral, or intravenous corticosteroids) or immunomodulating agents within 4 weeks before the screening visit or during the screening period.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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24 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo will be given on Day 1 orally

Treatment:

Drug: Placebo

Vitamin D

Active Comparator group

Description:

Administration of 500,000 IU Vitamin D orally on Day 1

Treatment:

Drug: Vitamin D